Role of purine nucleotide receptor signaling in P. falciparum invasion of erythrocytes.

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K08450
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Koshino Ichiro 東京女子医科大学, 医学部, 講師 (80328377)
• Co-Investigator(Kenkyū-buntansha): 新敷 信人 東京女子医科大学, 医学部, 助教 (80569658)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Keywords: マラリア / 赤血球 / cAMP

Outline of Final Research Achievements

Malaria is one of the major three infectious diseases in the world, caused by infection by malaria parasites. This study was conducted to examine if ATP-mediated intracellular signaling in host erythrocytes is critical in parasite infection, and to establish the basis for therapeutic strategy to prevent the parasite invasion of erythrocytes by interrupting the signaling pathway.
Contrary to the expectation, all reagents examined which interrupt ATP-mediated signaling failed to inhibit parasite invasion. However, several reagents that leads to elevation in intracellular cyclic AMP level inhibited parasite invasion.
These findings give some basis for therapeutic strategy by increasing cyclic AMP level exclusively in erythrocytes.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

世界規模での精力的な研究にも関わらずマラリアが甚大な人的被害をもたらし続けている理由は、マラリア原虫の高頻度な遺伝子変異による薬剤耐性の獲得である。
遺伝子変異の恐れが全くない宿主赤血球を標的とし、細胞内サイクリックAMP濃度を上昇させることによってマラリア原虫の感染を抑制できることを示した本研究の成果は、薬剤耐性の発生が事実上起こり得ない全く新規の治療法を確立するための基盤となる非常に重要な知見である。